Autosomal-dominant Hyper-IgE SyndromePhase 2NCT02996448
Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome
A Phase 2 study testing NDV-3A in people with Autosomal-dominant Hyper-IgE Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: AD-HIES is a disease that weakens the immune system. It puts people at risk for infections, particularly Staph and Candida infections. Researchers want to test a vaccine that may help keep people from getting these infections, which would help people with AD-HIES. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Autosomal-dominant Hyper-IgE Syndrome
- What is being tested?
- NDV-3A
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2016to 9 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-55 years.
- For healthy volunteers: in general good health, without significant medical illness, physical exam findings, or significant laboratory abnormalities as determined by the investigator.
- For participants with AD-HIES: confirmation of diagnosis with a STAT3 mutation.
- Participants who can get pregnant must be willing to use an acceptable form of contraception for the duration of participation and have a negative pregnancy test at screening.
- Agree to allow storage of biological samples for future research.
Who cannot join
- Has a history of allergic response or other serious reaction to aluminum and/or yeast products.
- Has a history of clinically significant allergy including anaphylaxis or other serious reaction to food, vaccines, or other drugs, that in the opinion of the investigator, might put the participant at undue risk.
- Has an active infection (such as S aureus abscess, pneumonia, acute Candida mucocutaneous infection). Baseline state of chronic infections will be considered by the PI (eg, chronic Pseudomonas infection in lung).
- Has an active infection with hepatitis B, hepatitis C, or HIV.
- Has received or is planning to receive any investigational drug, investigational vaccine, or investigational device within four weeks prior to vaccination, or at any other time during their participation in the study.
- Has received or is planning to receive any other live vaccine within three weeks before vaccination or for three weeks after vaccination.
Show all 23Show fewer
- Self-reported current alcohol abuse or addiction.
- Self-reported current illicit drug abuse or addiction, or drug screen positive for illicit drugs.
- Current or planned use, within 3 weeks before vaccination, of any medications or treatments that may alter immune responses to the study vaccine (eg, immunosuppressive medications including systemic corticosteroids, cyclosporine, tacrolimus, cytotoxic drugs, Bacillus Calmette-Guerin, monoclonal antibodies, or radiation therapy). Topical, intranasal, or inhaled immunosuppressants such as corticosteroids will be allowed.
- Current or planned use within 2 weeks before vaccination of immune globulin replacement.
- Has any of the following laboratory abnormalities at the screening visit:
- Alanine transaminase (ALT), aspartate transaminase (AST), and/or alkaline
- phosphatase (ALP) > 1.5 times the upper limit of normal (ULN).
- Total bilirubin level > 1.5 times the ULN
- Serum creatinine level > 1.5 times the ULN
- Absolute neutrophil count < 750 cells/microliter
- Hemoglobin < 9 mg/dL
- Platelet count < 100,000
- Refusal or inability to comply with study procedures to the extent that it is potentially harmful to the participant or to the integrity of the study data.
- Has donated blood/plasma within four weeks before vaccination.
- Is pregnant or breastfeeding, or intends to become pregnant over the course of the study.
- Is unable to commit to the follow-up visits and or has unreliable access to a telephone for follow-up contacts, either by self-admission (self-reporting) or in the opinion of the investigator.
- Any other condition the investigator believes would interfere with the participant s ability to provide informed consent, comply with study instructions, or that might confound the interpretation of the study results or put the participant at undue risk.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Phase 2a Study to Evaluate the Safety, Tolerability, and Immunogenicity of One Dose of NDV-3A Vaccine in Patients With STAT3-Mutated Hyper-IgE Syndrome
Background:
AD-HIES is a disease that weakens the immune system. It puts people at risk for infections, particularly Staph and Candida infections. Researchers want to test a vaccine that may help keep people from getting these infections, which would help people with AD-HIES.
Read more
Objective:
To test the new vaccine NDV-3A for protection against infection from the yeast Candida and the bacterium Staphylococcus aureus (Staph).
Eligibility:
Adults ages 18-55 who have AD-HIES
Healthy volunteers ages 18-55
Design:
Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone in between some visits.
Participants will be screened with a medical history, physical exam, and blood and urine tests.
Participants will have 2 baseline visits. They will have repeat the screening tests. They will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected. Vaginal and stool samples are optional. Any eczema on their skin will be looked at.
Participants will fill out symptom diary cards to record how they feel.
Participants will have the NDV-3A vaccine injected into a muscle in the arm.
Participants will return the next 2 days. They will have a physical exam. Blood will be collected.
Participants will have 2 more follow-up visits at the NIH. They will have a physical exam. They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected. Vaginal and stool samples are optional.
Participants will be called once a month for 5 months after the vaccination. There is an optional visit about 6 weeks after the vaccination. Participants will provide a blood sample at this visit.
Read the detailed description
Autosomal-dominant hyper-IgE syndrome (AD-HIES) is characterized by recurrent Staphylococcus aureus and Candida epithelial infections, which is thought to be due, in part, to a lack of Th17 cell differentiation, thus impairing epithelial immunity. Treatment of AD-HIES is primarily supportive with prophylactic antibiotics; however, this is limited by microbial resistance and intolerance of medications, and infections do still occur. Immunological intervention with a vaccine could improve quality of life by preventing these infections altogether.
The NDV-3A vaccine consists of a recombinant protein derived from the Candida Als3 adhesion protein. This protein is homologous to surface proteins on S aureus and has been shown in preclinical studies to protect against both intravascular and subcutaneous challenge with S aureus. Therefore, NDV-3A represents not only the first antifungal vaccine, but also the first vaccine to provide cross-kingdom protection. In Phase 1 and Phase 2 studies in healthy volunteers (150 receiving vaccine), the safety profile of this vaccine is very reassuring as the vaccine elicits a strong antibody response after a single dose in all vaccinees as well as a Th1 and/or Th17 response in the majority of vaccinees. We will enroll 20 healthy adult volunteers and 20 adults with AD-HIES in an open-label, single-dose study to assess the immunological response to and the safety/tolerability of the NDV-3A vaccine. We anticipate an increase in baseline anti-Als3 IgG within 2 weeks post-vaccination.
- Conditions
- Autosomal-dominant Hyper-IgE Syndrome
- Being tested
- NDV-3A
- Keywords
- AD-HIES, Anti-rAls3 Antibody, Staphylococcus Aureus, Candida Albicans, RNA Transcriptome
- Medical subject headings
- Job Syndrome, Staphylococcal Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NDV-3ADrug
A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.
| Study group | Role | What they receive |
|---|---|---|
| NDV 3A vaccine | Experimental | Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection. Receives: Drug: NDV-3A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.
Antibody titer
Measured: 2 weeks after vaccination
Secondary outcomes (2)
Number of Participants With Serious Adverse Events That Led to Study Termination.
Measured: Up to 6 months
Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2016 (estimated)
- Study start17 Nov 2016
- Primary completion22 Jul 2018
- Study completion9 Oct 2018
Why it stopped: Safety concerns led to early termination.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autosomal-dominant Hyper-IgE SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Alexandra Freeman, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02996448
- Sponsor's protocol ID
- 170017
- Other IDs
- 17-I-0017
- Status last verified
- Oct 2018
- First submitted
- 16 Dec 2016
- Last updated
- 30 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
Publications
Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.
PubMed 22268731Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR, Edwards JE Jr. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006 Jul 15;194(2):256-60. doi: 10.1086/504691. Epub 2006 Jun 6.
PubMed 16779733Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011 Feb;10(2):168-73. doi: 10.1128/EC.00279-10. Epub 2010 Nov 29.
PubMed 21115738
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Study to Evaluate the Safety, Tolerability, and Immunogenicity of One Dose of NDV-3A Vaccine in Patients With STAT3-Mutated Hyper-IgE Syndrome
- ClinicalTrials.gov ID
- NCT02996448
- Acronym / sponsor ID
- 170017
- Conditions
- Autosomal-dominant Hyper-IgE Syndrome
- Keywords
- AD-HIES, Anti-rAls3 Antibody, Staphylococcus Aureus, Candida Albicans, RNA Transcriptome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Safety concerns led to early termination.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 17 Nov 2016
- Primary completion
- 22 Jul 2018 (actual)
- Study completion
- 9 Oct 2018 (actual)
- First posted
- 19 Dec 2016 (estimated)
- Results
- Posted 30 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
AD-HIES is a disease that weakens the immune system. It puts people at risk for infections, particularly Staph and Candida infections. Researchers want to test a vaccine that may help keep people from getting these infections, which would help people with AD-HIES.
Objective:
To test the new vaccine NDV-3A for protection against infection from the yeast Candida and the bacterium Staphylococcus aureus (Staph).
Eligibility:
Adults ages 18-55 who have AD-HIES
Healthy volunteers ages 18-55
Design:
Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone in between some visits.
Participants will be screened with a medical history, physical exam, and blood and urine tests.
Participants will have 2 baseline visits. They will have repeat the screening tests. They will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected. Vaginal and stool samples are optional. Any eczema on their skin will be looked at.
Participants will fill out symptom diary cards to record how they feel.
Participants will have the NDV-3A vaccine injected into a muscle in the arm.
Participants will return the next 2 days. They will have a physical exam. Blood will be collected.
Participants will have 2 more follow-up visits at the NIH. They will have a physical exam. They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected. Vaginal and stool samples are optional.
Participants will be called once a month for 5 months after the vaccination. There is an optional visit about 6 weeks after the vaccination. Participants will provide a blood sample at this visit.
Detailed description
Autosomal-dominant hyper-IgE syndrome (AD-HIES) is characterized by recurrent Staphylococcus aureus and Candida epithelial infections, which is thought to be due, in part, to a lack of Th17 cell differentiation, thus impairing epithelial immunity. Treatment of AD-HIES is primarily supportive with prophylactic antibiotics; however, this is limited by microbial resistance and intolerance of medications, and infections do still occur. Immunological intervention with a vaccine could improve quality of life by preventing these infections altogether.
The NDV-3A vaccine consists of a recombinant protein derived from the Candida Als3 adhesion protein. This protein is homologous to surface proteins on S aureus and has been shown in preclinical studies to protect against both intravascular and subcutaneous challenge with S aureus. Therefore, NDV-3A represents not only the first antifungal vaccine, but also the first vaccine to provide cross-kingdom protection. In Phase 1 and Phase 2 studies in healthy volunteers (150 receiving vaccine), the safety profile of this vaccine is very reassuring as the vaccine elicits a strong antibody response after a single dose in all vaccinees as well as a Th1 and/or Th17 response in the majority of vaccinees. We will enroll 20 healthy adult volunteers and 20 adults with AD-HIES in an open-label, single-dose study to assess the immunological response to and the safety/tolerability of the NDV-3A vaccine. We anticipate an increase in baseline anti-Als3 IgG within 2 weeks post-vaccination.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NDV 3A vaccine | Experimental | Drug: NDV-3AParticipants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
Key exclusion criteria (23 listed)
- Has a history of allergic response or other serious reaction to aluminum and/or yeast products.
- Has a history of clinically significant allergy including anaphylaxis or other serious reaction to food, vaccines, or other drugs, that in the opinion of the investigator, might put the participant at undue risk.
- Has an active infection (such as S aureus abscess, pneumonia, acute Candida mucocutaneous infection). Baseline state of chronic infections will be considered by the PI (eg, chronic Pseudomonas infection in lung).
- Has an active infection with hepatitis B, hepatitis C, or HIV.
- Has received or is planning to receive any investigational drug, investigational vaccine, or investigational device within four weeks prior to vaccination, or at any other time during their participation in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NDV-3AA vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection. | Drug | NDV 3A vaccine |
Primary outcome
Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.
Time frame: 2 weeks after vaccination
Antibody titer
2 secondary outcomes
Number of Participants With Serious Adverse Events That Led to Study Termination.
Time frame: Up to 6 months
Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22268731Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.
- Background: PubMed 16779733Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR, Edwards JE Jr. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006 Jul 15;194(2):256-60. doi: 10.1086/504691. Epub 2006 Jun 6.
- Background: PubMed 21115738Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011 Feb;10(2):168-73. doi: 10.1128/EC.00279-10. Epub 2010 Nov 29.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexandra Freeman, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NDV-3A in people with Autosomal-dominant Hyper-IgE Syndrome, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer. (time frame: 2 weeks after vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02996448, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2020.